Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention‐deficit/hyperactivity disorder, obsessive–compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A ‘pathway’ driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the ‘gene–environment neuroscience interaction’. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench‐to‐bedside scientific discovery agenda with ongoing clinician and patient engagement.

Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders

Objectives Early developmental assessment is crucial for effective support and intervention. This study examined factors that contribute to (a) older child age when caregivers first became concerned about their child’s development and (b) older child age at the point of entry into developmental and diagnostic assessment. We also quantified how factors contributed to risk of children not receiving an assessment by 5 years and considered the acceptability of electronic data capture for families. Design This cross-sectional study collected information about caregiver developmental concerns, family history and child characteristics. Setting Children and families entered a large, publicly funded hospital-based paediatric developmental assessment service. Participants Consecutively enrolled children (N=916) aged 6 months to 17 years with neurodevelopmental concerns and their caregivers. Main outcomes and measures A developmental history questionnaire completed by caregivers. Results The average age that caregivers identified developmental concerns was 3.0 years of age but the average age of a receiving a developmental assessment was 6.6 years. Only 46.4% of children received a diagnostic assessment by 5 years of age, even though 88.0% of caregivers were concerned about their child’s development by that age. Parental age, relationship status, education level, prior use of support services and being from a culturally and linguistically diverse background contributed to age at identification of concern, age at diagnostic assessment and the likelihood of receiving a diagnostic assessment by 5 years. Electronic data capture had high acceptability, with 88.2% of caregivers reporting a preference for electronic completion of questionnaires. Conclusions The study shows a substantial delay in diagnostic assessments that leaves most vulnerable children without an assessment by school age and highlights contributors to delays. These delays highlight the complexity of delivering early intervention and support policies that rely on swift and appropriate developmental assessment to vulnerable families.

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Diagnostic delay in children with neurodevelopmental conditions attending a publicly funded developmental assessment service: findings from the Sydney Child Neurodevelopment Research Registry

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Delineating early developmental pathways to ADHD: Setting an international research agenda

Clinical staging is now recognized as a key tool for facilitating innovation in personalized and preventative mental health care. It places a strong emphasis on the salience of indicated prevention, early intervention, and secondary prevention of major mental disorders. By contrast to established models for major mood and psychotic syndromes that emerge after puberty, developments in clinical staging for childhood-onset disorders lags significantly behind. In this article, criteria for a transdiagnostic staging model for those internalizing and externalizing disorders that emerge in childhood is presented. This sits alongside three putative pathophysiological profiles (developmental, circadian, and anxious-arousal) that may underpin these common illness trajectories. Given available evidence, we argue that it is now timely to develop a transdiagnostic staging model for childhood-onset syndromes. It is further argued that a transdiagnostic staging model has the potential to capture more precisely the dimensional, fluctuating developmental patterns of illness progression of childhood psychopathology. Given potential improvements in modelling etiological processes, and delivering more personalized interventions, transdiagnostic clinical staging for childhood holds much promise for assisting to improve outcomes. We finish by presenting an agenda for research in developments of transdiagnostic clinical staging for childhood mental health. 

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Transdiagnostic Clinical Staging for Childhood Mental Health: An Adjunctive Tool for Classifying Internalizing and Externalizing Syndromes that Emerge in Children Aged 5–11 Years

Behavioural and language difficulties co-occur in multiple neurodevelopmental conditions. Our understanding of these problems has arguably been slowed by an overreliance on study designs that compare diagnostic groups and fail to capture the overlap across different neurodevelopmental disorders and the heterogeneity within them.We recruited a large transdiagnostic cohort of children with complex needs (N = 805) to identify distinct subgroups of children with common profiles of behavioural and language strengths and difficulties. We then investigated whether and how these data-driven groupings could be distinguished from a comparison sample (N = 158) on measures of academic and socioemotional functioning and patterns of global and local white matter connectome organisation. Academic skills were assessed via standardised measures of reading and maths. Socioemotional functioning was captured by the parent-rated version of the Strengths and Difficulties Questionnaire.We identified three distinct subgroups of children, each with different levels of difficulties in structural language, pragmatic communication, and hot and cool executive functions. All three subgroups struggled with academic and socioemotional skills relative to the comparison sample, potentially representing three alternative but related developmental pathways to difficulties in these areas. The children with the weakest language skills had the most widespread difficulties with learning, whereas those with more pronounced difficulties with hot executive skills experienced the most severe difficulties in the socioemotional domain. Each data-driven subgroup could be distinguished from the comparison sample based on both shared and subgroup-unique patterns of neural white matter organisation. Children with the most pronounced deficits in language, cool executive, or hot executive function were differentiated from the comparison sample by altered connectivity in predominantly thalamocortical, temporal-parietal-occipital, and frontostriatal circuits, respectively.These findings advance our understanding of commonly co-morbid behavioural and language problems and their relationship to behavioural outcomes and neurobiological substrates. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcpp.13685

Transdiagnostic profiles of behaviour and communication relate to academic and socioemotional functioning and neural white matter organisation

A national harmonised data collection network for neurodevelopmental disorders: A transdiagnostic assessment protocol for neurodevelopment, mental health, functioning and well-being

Phillipa Quinn

Papers

A national harmonised data collection network for neurodevelopmental disorders: A transdiagnostic assessment protocol for neurodevelopment, mental health, functioning and well-being